Waterhemp (Amaranthus tuberculatus) is a common and troublesome weed in cropping systems throughout the United States. With the potential for future periods of low rainfall or drought, the need for improved weed control under drought stress is necessary. Drought stress typically reduces herbicide efficacy by reducing the foliar uptake of herbicides and their translocation. The objectives of this research were to determine the efficacy of 2,4-dichlorophenoxyacetic acid (2,4-D) and glyphosate, applied alone or when tank-mixed, on waterhemp under varying levels of drought stress, the effect of the timing of drought stress in relation to herbicide application and the absorption and translocation of each herbicide in drought-stressed waterhemp. At reduced herbicide rates, 2,4-D had a greater level of control of waterhemp under drought stress, compared to glyphosate. The level of herbicide efficacy was lower when the amount of water that was applied to the plants was reduced. The level of waterhemp control was greatest when drought stress occurred before the herbicide application and when the plants were watered to saturation after the application, compared to when drought stress occurred after the herbicide application or restricted watering levels occurred throughout the entire study. Glyphosate absorption and translocation were reduced in the drought-stressed plants, but 2,4-D absorption and translocation were not altered. The absence of a reduction in 2,4-D translocation in the drought-stressed weeds has not been previously reported. Applying herbicides prior to a rainfall event could increase the weed control level, even if the weed is stressed. Determining how and why 2,4-D absorption and translocation levels, compared to those of glyphosate, are unaffected by drought stress in waterhemp can aid in improving the control of drought-stressed weeds with other postemergence herbicides.